Germline mutation landscape of DNA damage repair genes in African Americans with prostate cancer highlights potentially targetable RAD genes.

Black or African American / genetics DNA Damage / genetics Germ-Line Mutation Humans Male Mutation Prostatic Neoplasms / genetics

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
15 03 2022
Historique:
received: 02 05 2021
accepted: 18 02 2022
entrez: 16 3 2022
pubmed: 17 3 2022
medline: 6 4 2022
Statut: epublish

Résumé

In prostate cancer, emerging data highlight the role of DNA damage repair genes (DDRGs) in aggressive forms of the disease. However, DDRG mutations in African American men are not yet fully defined. Here, we profile germline mutations in all known DDRGs (N = 276) using whole genome sequences from blood DNA of a matched cohort of patients with primary prostate cancer comprising of 300 African American and 300 European Ancestry prostate cancer patients, to determine whether the mutation status can enhance patient stratification for specific targeted therapies. Here, we show that only 13 of the 46 DDRGs identified with pathogenic/likely pathogenic mutations are present in both African American and European ancestry patients. Importantly, RAD family genes (RAD51, RAD54L, RAD54B), which are potentially targetable, as well as PMS2 and BRCA1, are among the most frequently mutated DDRGs in African American, but not in European Ancestry patients.

Identifiants

DOI: 10.1038/s41467-022-28945-x PMID: 35292633 PMC: PMC8924169
pubmed: 35292633
doi: 10.1038/s41467-022-28945-x
pii: 10.1038/s41467-022-28945-x
pmc: PMC8924169
doi:

Types de publication

Journal Article Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

1361

Informations de copyright

© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.

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Auteurs

Indu Kohaar (I)

Center for Prostate Disease Research, John P. Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences and the Walter Reed National Military Medical Center, Bethesda, MD, 20817, USA. ikohaar@cpdr.org.
Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, 20817, USA. ikohaar@cpdr.org.
ORCID: 0000-0003-4376-0432

Xijun Zhang (X)

The American Genome Center, Precision Medicine Initiative for Military Medical Education and Research (PRIMER), Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA.
Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA.

Shyh-Han Tan (SH)

Center for Prostate Disease Research, John P. Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences and the Walter Reed National Military Medical Center, Bethesda, MD, 20817, USA.
Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, 20817, USA.
ORCID: 0000-0001-8250-7005

Darryl Nousome (D)

Center for Prostate Disease Research, John P. Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences and the Walter Reed National Military Medical Center, Bethesda, MD, 20817, USA.
Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, 20817, USA.

Kevin Babcock (K)

Center for Prostate Disease Research, John P. Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences and the Walter Reed National Military Medical Center, Bethesda, MD, 20817, USA.

Lakshmi Ravindranath (L)

Center for Prostate Disease Research, John P. Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences and the Walter Reed National Military Medical Center, Bethesda, MD, 20817, USA.
Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, 20817, USA.

Gauthaman Sukumar (G)

The American Genome Center, Precision Medicine Initiative for Military Medical Education and Research (PRIMER), Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA.
Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA.

Elisa Mcgrath-Martinez (E)

The American Genome Center, Precision Medicine Initiative for Military Medical Education and Research (PRIMER), Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA.
Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA.

John Rosenberger (J)

The American Genome Center, Precision Medicine Initiative for Military Medical Education and Research (PRIMER), Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA.
Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA.
ORCID: 0000-0003-2914-6727

Camille Alba (C)

The American Genome Center, Precision Medicine Initiative for Military Medical Education and Research (PRIMER), Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA.
Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA.
ORCID: 0000-0002-0458-1629

Amina Ali (A)

Center for Prostate Disease Research, John P. Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences and the Walter Reed National Military Medical Center, Bethesda, MD, 20817, USA.
Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, 20817, USA.
Urology Service, Walter Reed National Military Medical Center, Bethesda, MD, 20814, USA.

Denise Young (D)

Center for Prostate Disease Research, John P. Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences and the Walter Reed National Military Medical Center, Bethesda, MD, 20817, USA.
Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, 20817, USA.

Yongmei Chen (Y)

Center for Prostate Disease Research, John P. Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences and the Walter Reed National Military Medical Center, Bethesda, MD, 20817, USA.

Jennifer Cullen (J)

Center for Prostate Disease Research, John P. Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences and the Walter Reed National Military Medical Center, Bethesda, MD, 20817, USA.

Inger L Rosner (IL)

Center for Prostate Disease Research, John P. Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences and the Walter Reed National Military Medical Center, Bethesda, MD, 20817, USA.

Isabell A Sesterhenn (IA)

Joint Pathology Center, Silver Spring, MD, 20906, USA.

Albert Dobi (A)

Center for Prostate Disease Research, John P. Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences and the Walter Reed National Military Medical Center, Bethesda, MD, 20817, USA.
Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, 20817, USA.

Gregory Chesnut (G)

Center for Prostate Disease Research, John P. Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences and the Walter Reed National Military Medical Center, Bethesda, MD, 20817, USA.
Urology Service, Walter Reed National Military Medical Center, Bethesda, MD, 20814, USA.

Clesson Turner (C)

The American Genome Center, Precision Medicine Initiative for Military Medical Education and Research (PRIMER), Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA.

Clifton Dalgard (C)

The American Genome Center, Precision Medicine Initiative for Military Medical Education and Research (PRIMER), Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA.
Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA.

Matthew D Wilkerson (MD)

The American Genome Center, Precision Medicine Initiative for Military Medical Education and Research (PRIMER), Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA.
Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA.

Harvey B Pollard (HB)

The American Genome Center, Precision Medicine Initiative for Military Medical Education and Research (PRIMER), Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA.
Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA.

Shiv Srivastava (S)

Center for Prostate Disease Research, John P. Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences and the Walter Reed National Military Medical Center, Bethesda, MD, 20817, USA.
Department of Biochemistry and Molecular & Cell biology, Georgetown University School of Medicine, Washington, DC, 20057, USA.
ORCID: 0000-0001-9014-8081

Gyorgy Petrovics (G)

Center for Prostate Disease Research, John P. Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences and the Walter Reed National Military Medical Center, Bethesda, MD, 20817, USA. gpetrovics@cpdr.org.
Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, 20817, USA. gpetrovics@cpdr.org.
ORCID: 0000-0003-3732-284X

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Classifications MeSH

questionsmedicales.fr › Personnes › Nord-Américains › Groupes de population aux États-Unis › Populations d'origine continentale › Noir ou Africain Américain › Germline mutation landscape of DNA damage...
questionsmedicales.fr › Phénomènes génétiques › Altération de l'ADN › Germline mutation landscape of DNA damage...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › Mutation germinale › Germline mutation landscape of DNA damage...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Germline mutation landscape of DNA damage...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › Germline mutation landscape of DNA damage...
questionsmedicales.fr › Maladies urogénitales › Tumeurs de l'appareil urogénital › Tumeurs de l'appareil génital mâle › Tumeurs de la prostate › Germline mutation landscape of DNA damage...